In vivo studies using cloned genetically defined mouse leukemia retroviruses administered to newborn mice of known backgrounds yielded data on pathogenicity of replication-competent Rauscher murine leukemia virus (R-MuLV), Moloney murine leukemia virus (M-MuLV), and their recombinants. R-MuLV is extremely pleiotropic, capable of inducing lymphoid, erythroid and granulocytic malignant neoplasms at approximately equal rates. M-MuLV is almost always lymphomagenic. M-MuLV/R-MuLV recombinants may resemble either parent or produce intermediate frequencies, depending on the segments of the genome represented in the hybrid. In vitro transformation experiments, using oncoviruses (with and without promoters) to infect normal primate cultures, continue to produce greatly altered morphologic and growth patterns; no fully malignant transformants have been proven to date. Human and animal xenografts on athymic nude mice have been used to study tumor progression, malignant transformation, and to characterize spontaneous cancer of particular theoretical or practical significance.